Impact of time-to-treatment on survival for early-stage non-small cell lung cancer in The Netherlands-a nationwide observational cohort study.

Abstract

Varied outcomes on the relation between time-to-treatment and survival in early-stage non-small cell lung cancer (NSCLC) patients are reported. We examined this relation in a large multicentric retrospective cohort study and identified factors associated with extended time-to-treatment. We included 9,536 patients with clinical stage I-II NSCLC, diagnosed and treated in 2014-2019, from the Netherlands Cancer Registry that includes nation-wide data. Time-to-treatment was defined as the number of days between first outpatient visit for suspected lung cancer and start of treatment. The effect of extended time-to-treatment beyond the first quartile and survival was studied with Cox proportional hazard regression. Analyses were stratified for stage and type of therapy. Time-to-treatment was adjusted for multiple covariates including performance status and socioeconomic status. Factors associated with treatment delay were identified by multilevel logistic regression. Median time-to-treatment was 47 days [interquartile range (IQR): 34-65] for stage I and 46 days (IQR: 34-62) for stage II. The first quartile extended to 33 days for both stages. Risk of death increased significantly with extended time-to-treatment for surgical treatment of clinical stage II patients [adjusted hazard ratio (aHR) >33 days: 1.36, 95% confidence intervals (CI): 1.09-1.70], but not in stage II patients treated with radiotherapy or in stage I patients. Causes of prolonged time-to-treatment were multifactorial including diagnostic tests, such as endoscopic ultrasound (EUS) or endobronchial ultrasound (EBUS). Clinical stage II patients benefit from fast initiation of surgical treatment. Surprisingly this appears to be accounted for by patients who are clinically stage II but pathologically stage I. Further study is needed on characterizing these patients and the significance of lymph node- or distant micrometastasis in guiding time-to-treatment and treatment strategy.